Diamond Blackfan Anemia (DBA) is an inherited bone marrow failure (BMF) syndrome that presents in infancy with red cell aplasia, sometimes with developmental abnormalities. In common with other (BMF) syndromes the BMF is variable and family members can carry the mutation but show mild or no BMF or, in other cases, patients can go into long lasting remission. We hypothesize that the variable penetrance and remission are due to somatic mutations in stem cells or multipotent progenitors that rescue cells from the effects of the inherited mutation, leading to clonal hematopoiesis and clinical remission. We believe that if we can determine the nature of these genetic changes they will increase our understanding of the pathogenesis of DBA and suggest potential drug targets that may be used in developing new treatments. We will isolate DNA from bone marrow and skin biopsies from 20 DBA patients, including some in clinical remission. We will determine genetic differences between the bone marrow sample and the skin sample from the same person to identify somatic mutations that have occurred in the bone marrow. This will be done using two approaches 1. High density SNP microarray analysis, to find genomic changes that will not be found by exome sequencing including copy number changes and acquisition of copy neutral loss of heterozygosity, where both copies of autosomal genes may derive from the same parent and 2. Whole exome sequencing to identify non-synonymous mutations in protein coding regions. Prior to functional studies, likely candidates for rescuing mutations will be further validated by re-sequencing in a second group of patients and bioinformatic analysis to assess their possible effects on hematopoiesis.